Post-Conference Perspectives: Update on PARP Inhibitors in Breast Cancer - Episode 3

Adding Olaparib to Chemotherapy in TNBC: The PARTNER Trial

Transcript:Joyce A. O’Shaughnessy, MD: The PARTNER trial is a very innovative ongoing phase III clinical trial in women with newly diagnosed triple-negative breast cancer [TNBC] that’s of the basal phenotype. The investigators are selecting the triple-negative patients who have a basal-like phenotype. Or if the women have triple-negative breast cancer and a germline BRCA mutation, they’re also eligible. And the goal of the trial is to see whether the addition of the PARP inhibitor, olaparib, to a platinum-based preoperative therapy regimen in triple-negative breast cancer will substantially increase the pathologic complete response rate. Because we know that a substantial improvement in the pathologic complete response rate does translate into improvement in event-free survival.

So in the first part of this trial, the carboplatin given every 3 weeks and weekly paclitaxel are being combined with olaparib in a couple of different schedules. You can’t give olaparib the day of chemotherapy, but it’s testing 2 different schedules of the olaparib to find the safest schedule of the olaparib with the carboplatin and the paclitaxel. And having found that, there are 500 or more patients being randomized to the carboplatin plus weekly paclitaxel, with or without the olaparib. The goal is to have an increase in the pathologic complete responses in the basal triple-negative population by 15% or more and the germline BRCA population by 20% or more. And that would be considered a successful trial, because at that level, you should be making an impact on overall event-free survival.

So it’s a very important trial, because the basal-like breast cancers are believed to have a homologous recombination deficiency. So that triple-negative subset really should benefit from the PARP inhibitor olaparib, and in the context of the DNA damage is being done by the carboplatin, the PARP inhibitor should inhibit repair and increase the effectiveness of the chemotherapy. And so that’s a very important hypothesis that we don’t know the answer to. This is a very important trial, and of course, we would expect it to help the germline BRCA population.

The only thing is that sometimes the platinum agents themselves are so effective in the context of homologous recombination deficiency that the addition of a PARP inhibitor may not increase the pathologic complete response rate. We saw that in the BrighTNess trial with another PARP inhibitor called veliparib. But veliparib has very weak PARP-trapping potency, while olaparib has high potency as a PARP-trapping PARP inhibitor. And so it’s very important to look at this hypothesis to see whether the PARP inhibitor will add to the pathological complete response rate above and beyond carboplatin. So, that’s purpose of this PARTNER trial.

Transcript Edited for Clarity